The report serves to carry out a detailed techno market evaluation of Biosaefty products and technologies with a view to identify the viable technology options available to India and determine the investment needs for implementing safety technologies. The basic contention of the report is that although bio safety technologies o not appear to be commercially viable in the short run, they do have the potential for a major impact in the human health and environmental management. The objective of the report is to come up with effective recommendations course of action to implement biosafety technologies given current infrastructure constraints and knowledge gaps in mind.

The scope of the study:

The scope of the report covers the current status of bio processing industry in the country including all segments and level of activities and the future trends. It identifies the current biosafety technology status in the country both in terms of software and hardware and compares it with international levels. The report tries to assess the hazards and risks associated with specific bio processing areas through past case studies. It delves into the current regulations, legislation and code of practices of India and various other countries/ agencies and tries to identify the limitations of our guidelines and infrastructure in implementing these guidelines. An idea about international infrastructure on bio safety and risk assessment is provided. He report spells out the bio safety strategies and technologies keeping in mind the relevant Indian and international regulations and guidelines and experiences of various expert groups. The strategies have been separately outlined for research laboratories, hospitals, large industrial processing and agricultural and environmental applications. The total investment needs for bio safety related activities have been assessed and the benefit estimated. It outlined specific recommendations and course of action for various agencies.

Importance of the topic:

At present level there are large uncertainties in anticipating the consequences of the introduction of novel organism in the environment due to major gaps in the knowledge. In facts considerable speculation and debate all over the world about the potential risk and benefits associated with biotechnology and the extent of control measures to be adopted to counter the risks. The potential environmental risks associated with the new bio technologies are best described as, low probability, high consequence risks, that is while , there is only a small possibility that damage could occur, that damage that could occur is great commercial production of biotechnology productions in the country is expect to double to around Rs. 5500 crores by the turn of the century with an envisaged investment of around Rs 1000 crores with around 15% of investment in rDNA based research and production. Indeed for a new technology characterized by a low probability of causing harm, the early stages of development need cause little worry, but, as the technology becomes more widely used and it moves in new directions, the likelihood of underside consequences increase, the chemical industrial can be taken as example, when only few chemical were in daily use their production was low there was no hazard for society. The issue of human health risk and ecological perturbation became only too evident, however when the production of chemicals increased. Biotechnology is an area where several areas related to risk assessment and safety remain to be answered ad the history / case studies of past hazards makes it all the more necessary to take all the precautions with his industry. A detailed study addressing various issues and aspects of bio safety will go a long way in helping industry to strike a balance between the twin objectives of allowing society to benefit from new products of biotechnology and at the same time minimizing risks to public health and the environment.

The methodology:

The methodology for the survey has included both secondary and primary survey. Published information involving more than 300 articles in international magazines, journals, reports, seminar proceedings, books have been researched during the secondary survey. A thorough surfing of internet has been done to get information on various aspects of bio safety. In fact there is huge amount of information available on the subject. For the purpose of primary survey, direct as well as indirect contacts have been established through structured questionnaires wit several agencies both in India and abroad. There are several research/ academic institutes, colleges, hospitals and industries in India who are working wt micro organisms both conventional and genetically engineered (including rDNA) covering wide range (Pathogenic and non pathogenic). Keeping this scenario in mind a carefully researched sample had been drawn to cover different organizations working in this area in India including government departments, academic institutes, research labs ad cross section of bio tech industry. Most of them have been contacted directly. Around 40 research and manufacturing establishments including hospitals were contacted for detailed safety audit. The response received from some of the agencies have helped us in evaluation and formulating our recommendations. Large amount of research work/ large scale processing using newer techniques is being carried in the countries like US, Germany, UK an Japan. Several guidelines and code of practices for specific products have been outlined in these countries by different agencies. A cross section of agencies contacted have provided valuable information.

Study Limitations

Total lack of information and record maintenance on the part of domestic agencies had made the process of safety assessment a formidable task. Internationally also few surveys have been done on occupational diseases related to bio processes. Obtaining information from international sources has its own problems and only general information is available. Due to confidential nature of research work and also the sensitivity associated with generic engineering, the government authorities do not wish to disclose the details of the projects and research work being undertaken in this area. It is difficult to carry cost benefit analysis for the biosafety technologies due to paucity of information, novelty of the subject, lack of consensus on safety regulations and risk assessment and poor data base and experience.

Major Observations, Findings and Recommendations

Biotechnology Definition:

“The use of development of techniques using organisms (or parts of organisms) to provide or improve goods and services”.

Bio tech Industry Status:

The biotechnology industry embraces many sectors of the global economy. Sectors like Drugs and pharmaceuticals, food and agriculture, chemicals, energy and environment are harnessing tremendous benefits of biotechnology. The global market which was estimated at $9 bn in 1991 today stands at almost $20 bn. The current Indian market for biotechnology based products is estimated at Rs. 2700 crores. The technology emphasis in developed countries is fast switching to rDNA techniques. The Indian biotechnology industry is solely based on conventional bio technologies. Currently around 360 organisations are involved in Bio technology based activities, with bulk share with medicine and agriculture activities. The rDNA products are still at the research stage and market demand is generally met through imports especially for vaccines, diagnostic products, therapeutic proteins, and high yielding planting materials etc. The bulk of the R&D resources for product development are currently being provided by the govt. The current consumption of bioech products will almost double in next 5 yrs. The expected additional investment is anticipated to be close to Rs.1000 crores in the next 8 to 10 yrs. The investments in large rDNA based projects in the next 5 to 8yrs will however remain mostly on peripheries.

Bio tech Industry Hazards and risk assessment

The major hazards of bio technology are those associated with exposure to large concentration of aerosolized micro organisms or their products. The concerns raised by industrial applications or bio technology involve hazards that might arise at different levels:

1) Hazards at the Laboratory and pilot plant stage
2) Hazard associated with industrial processing and by products handling
3) Hazard associated with the products obtained
4) Hazard with agricultural and environmental applications

The various hazards applicable to different bio technology processes are sumamrised in the table:

Bio tech Application

Hazards

Laboratory

Infections due to

Handling of micro organisms

Working with infectious agents

Industrial processing using rDNA based micro organisms

In advertent release of recombinant organisms in the factory and surrounding environment due to

The purpose of the risk management in bio technology is to assign appropriate control measures or containment measures commensurate with the estimated hazards of the micro-organisms both conventional and genetically modified. Based on the nature of hazards posed by the bio technological processes and some of the consequences as available from the past experience, the classification of infective micro-organisms are drawn up under 4 risk groups in increasing order of risk.

At lab scale, containment is assigned according to the hazard of the substances i.e. the GMO. At large scale, containment is assigned on the basis of the risk which incorporates the hazard and the potential for the GMO exposure from the process equipment.

Internationally a flexible approach to large scale containment in terms of unit operations of the process is advocated to take account of the diverse range of equipment, processes and type of hazards from the GMO. The concept of selecting appropriate containment levels commensurate with the level of risks at particular stage of processing is another feature of large scale contained use of GMOs.

The major concern of biotechnology is not so much from laboratory or large scale manufacturing but from agricultural and environmental applications where the risks are of far different dimensions. In such applications the risks associated with environmental releases of genetic engineered organisms are not always easily identified or quantified. The risks are not fixed ones, which we can ascertain from the beginning and apply to all introductions. A whole spectrum of introductions exists, from benign to potentially dangerous. The difficulties arise because of:

Lack of sufficient reliable data, particularly on long-term dangers.

Entirely different types of risk, and experiments required to measure it, form one case to the next. Assessments on gene A in rice have nothing to do with those on gene B in rice or gene C in tilapia, etc.

Difficulty in predicting the fate of released organisms or genes. Too little is know about gene and organism interactions.

The risk assessment is based on the past experience and case to case analyse the components of risk analysis are hazard identification, dose response assessment, exposure assessment and risk characterization.

Though there is considerable speculation and debate on the potential risks, there is now clear consensus among large segment of biotechnology community that for introduced genetic material or organisms probabilities of survival, multiplication, gene transfer, dispersal and detrimental effects are quite small and therefore the probability of the final event in the sequence is even smaller. The potential environmental risks associate with the introduction of new or novel organisms into an ecosystem are best described as ‘low probability’, high consequence risks’. The risks associated with genetically engineered organisms are considered to be of the same kind as that from introductions of non engineered organisms and organisms modified by other methods.

Bio safety regulations and guidelines:

In response to concerns about environmental introductions of GMOs, the countries world over have outlined policies and regulations for overseeing safety and environmental use of the products at every stage of the development of biotechnology products or services. For example at the research stage, control exists to help ebnsure the safety and well being of laboratory workers inclduinh controls on the manipulation and release of genetically engineered organisms. Legislation covers good lab and manufacturing practices and animal experimentation. At the production stage thee are important laws on the health and safety pf technical staff and other workers are important laws on the health and safety of technical staff and other workers as well as on product testing and analysis. Finally there are important laws which govern all bio technological processes which may cause emissions of harmful organisms. These laws are widely applied to all industrial processes, but are of particular importance to those using new technologies (e.g. based on rDNA). These regulations are under continuous review and modifications in light of new experiences. The regulations aim at striking balance and minimizing risks to public health and the environment. The guidelines employ the concept o physical and biological containment and also upon the principle of good laboratory practice.

Current Safety technology Status –India

We personally carried a broad safety audit of 32 organisations covering all category (low risk to high risk) and segments (manufacturing, research and services) of bio processing industry. The performance was measures on 8 different attributes, namely:

The performance of the organizations on various attributes have been expressed schematically in the next page. Generally it has been observed that the current safety practices in the bio tech industry in the country is less than satisfactory. Among the worst offenders are medical colleges and hospitals. The level of housekeeping, HRD practices and emergency planning are found to be lacking in most of the organizations. None of the organizations are found to have formulated any safety manual or to be maintaining any safety records. Many establishments are without adequate primary and secondary containment systems. Few organizations were totally unaware of guidelines and its implementation mechanisms. The organizations working with rDNA techniques have been found to be more safety conscious probably due to formal guidelines and level of consciousness.

Bio safety technology infrastructure is currently evolving in the country. Most of the safety equipment are available in the country. However imports takes place for high quality processing equipment with built in safety features. The total current imports has been estimated at around Rs.6.3 crores /yr. In the country equipment manufactured for other industries find use for bio tech applications which may not be desirable. There are no standards and test specifications in the country for bio processing equipment. Neither are there any special training programme, seminars, data bases and auditing firms on bio safety in the country. Internationally excellent data bases, training programmes, courses and reports have ben developed on various aspects of biosafety. Government has yet to address completely the issues on bio diversity and biosafety by offering any incentive or package for the industry. Internationally number of countries, agencies (especially UN agencies) and study groups have done commendable work on specific regulations and code of practices for different bio tech areas, environmental risk assessment, bio diversity, biosafety issues, equipment standards and economic impact studies. The country can immensely benefit from co-ordinating with various agencies.

Viable Biosafety Technologies:

It is very difficult to exactly assess the techno economic viability of biosafety technologies because of lack of consensus on the risks associated with bio processes, extent of containment/ control measures required and expected benefits. Even though the commercial viability of bio safety technology do not appear to be commercially viable due to low probability of any damage, however since the damage if it occurs may be so great, the safety will have to be of paramount importance. The safety issues of bio technology in a way parallels that in civil aviation and nuclear power sectors where the consequences of damage if it occurs is significant.

The viable Bio safety technologies and practices for applications at different levels i.e. research, large-scale processing and agricultural and environmental applications is based on the existing regulations and the consensus of group of experts. For different bio safety levels have been considered for bio tech laboratories, each consisting of combination of laboratory practices and techniques, safety equipment, and laboratory facilities. Each combination is specifically appropriate for the operations performed, the documented or suspected routes of transmission of the infectious agents, and for the laboratory function or activity. The recommended biosafety level for an organism represents the conditions under which the agent can be ordinarily handled safely. Process biosafety at large scale is mix of good operating practice, reliable and well maintained equipment and good equipment design arrived after striking a balance between the GMO hazard and the control measures.

There is limited experience with respect to genetically engineered organisms used in the environment and their effects. Organizations use a detailed pre-release evaluation process that draws upon a broad range of scientific expertise to review proposals for field test on a case basis. Although genetically engineered micro-organisms can not be completely contained at the field test site, a variety of control measures are available to limit their dispersal and impact. These include setting physical barriers at the test sites and selecting organisms with vulnerable biological features. Choosing the appropriate degree of control involves a trade-off between minimizing risk and maximizing the realism and their usefulness, of the field test.

Expected Market for Bio Safety Technology

It has been estimated that total investment needs to make biotechnology industry safe would be of the order of Rs 143 crores (safety features, equipment etc.) over the next 10 yrs. The actual investment in the safety equipment based on expected penetration is expected to be Rs.50 crore in the yr. 1996-2000 and Rs. 73 crores in the yr. 2000-05. The consumption of safety consumables (gloves, masks, clothes, goggles etc.) is expected to be substantial of the order of Rs. 72 crores and Rs. 190 crores during these periods. Almost 66% of the total requirement for equipment and consumable will arise from large scale processing and 23% from hospitals with balance from research institutes. The major equipment required will be autoclaves, incinerators, biosafety cabinets, laminar hoods etc. In addition there will be an annual expenditure on safety related training programmes, seminars, courses, audits and system designing estimated at Rs. 30 to 40 lakhs/ yr initially.

It is impossible to work out the exact benefits to the society. However based on a case study on laboratory based infections, it is estimated that it takes around 20 yrs to recover the investment in terms of savings in treatment costs and other indirect savings. However the intangible factors like ethical and social considerations have not been taken account of and when they are considered it may be impossible to go without adequate safety provisions. In case of environmental applications analyzing even few restricted issues related to risk assessment and commercialization pose such formidable challenge, that striking a balance between benefits of new technologies and minimizing risks to public health and environment can not even be attempted at present and it is better to err on the side of having more restrictive guidelines and control measures and gradually ease with experience.

Recommended Course of Action:

In order to introduce bio safety technologies and practices in the country :

An effective mechanism has to be worked out to exchange information on various biosafety and environmental risks aspects with international agencies.

There is need for periodic review of the guidelines and formation of effective physical monitoring system.

The guidelines have to address specific areas of biotechnology and also cover techniques other than rDNA. The emphasis will have to be on product rather than process of manufacture.

Of specific need us to build a strong awareness campaign in the country, demonstration projects and economic impact studies.

An effective infrastructure will have to be created with respect to standards, safety audits, bio safety courses, seminars, training programmes, equipment base etc.

Industry will have to be more conscious about safety and make serious efforts involuntarily implement national and international guidelines and practices.

Government has a large role to play and should conduct studies on environmental risk assessment and long term health impact and come out with specific financial and incentive package for the industry since the safety technologies on their own may not be financially viable for the industry.